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PHYSIOLOGICAL PROPERTIES OF HEART

June 18, 2024

PHYSIOLOGICAL PROPERTIES OF HEART. ELECTROCARDIOGRAPHY INVESTIGATION OF HEART. HEART AS A PUMP.

1. Morphology and functional organization of heart

a) Structure of heart. The heart contains four chambers: two upper atria, which receive venous blood and two lower ventricles, which eject blood into arteries. The right ventricle pumps blood to the lungs, where the blood becomes oxygenated. The left ventricle pumps oxygenated blood to the entire body.

The right and left atria receive blood from the venous system. The right atrium and ventricle are separated from the left one by septum, which is the muscular wall. This septum normally prevents mixture oxygenated and not oxygenated blood.

Between the atria and ventricles there is a layer of dense connective tissue known as fibrous skeleton of the heart. The connective tissue of skeleton also forms rings, called annuli fibroses around two pairs of one-way valves.

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b) Structure of myocardium. Bundles of myocardial cells in the atria attach to the upper margin of this fibrous skeleton and form a myocardium. The myocardial cell bundles of the ventricles attach to the lower margin and form a different myocardium. As a result, the myocardium of the atria and ventricles are structurally and functionally separated from each other.

Weight of whole myocardium consist 250-300g. Atria myocardium has two layers of muscle cells – circular and

longitudinal. Circular cells layers surround mouth of vessels, which fall into atria and may cover again it in constriction.

Ventricles myocardium has three layers of muscle cells. External and internal layer have spiral form and are common for both ventricles. Middle layer has circular orientation and is separated in every ventricle.

c) Functional specialties of myocardial cells. Myocardial cells contain actin and myosin filaments and contracts by means of the sliding filament mechanism. Myocardial cells are joined by gap junctions, due to which electrical impulses can spread to all cells in the mass. Sarcoplasmatic reticulum in myocardial cells is developed slightly. That is why some amount of calcium may enter the myocardial cell from the outside.

Besides contractive myocardial cells there are modified cells of the conduction system of the heart. They can generate and conduct impulses through myocardium.

d) Electrophysiological properties of the contractive myocardium. The main electrophysiological properties of the contractive myocardium are automaticity, contractility, conductability and excitability.

Automaticity is property to contract replying to electrical impulses, originated in pacemaker cells of the conduction system of the heart.

Contractility is property to contract replying to irritation.

Conductibility is property to spread electrical impulses through the conduction system and contractive myocardium.

Excitability is property to reply the irritation.

2. Automaticity of the heart

a) Structure of conduction system.

Specialized excitatory and conductive system of the heart: consists of:

1. Sinus node “SA” node: also called sinoatrial node, located in the right atrium. It is concerned with the generation of rhythmical impulse; it is the pacemaker of the heart that initiates each heart beat. This automatic nature of the heart beat is referred to as automaticity.

2. Internodal pathways conduct the impulse generated in SA node to the AV node.

3. The AV node (atrioventricular node), located near the right AV valve at the lower end of the interatrial septum, in the posterior septal wall of the right atrium. At which impulse from the atria is delayed before passing into the ventricles.

4. The AV bundle (bundle of His) conducts the impulse from the atria into ventricles.

5. The left and right bundles of purkinje fibers, which conduct the cardiac impulse to all parts of the ventricles. The purkinje fibers distribute the electrical excitation to the myocytes of the ventricles.

Figure: The cardiac conduction system.

Figure: organization of the AV node.

The SA node as the pacemaker of the heart: (Automaticity & rhythmicity)

Automaticity is the property of self-excitation (i.e. the ability of spontaneously generating action potentials independent of any extrinsic stimuli) while rhythmicity is the regular generation of these action potentials. In other words, the cardiac impulse normally arises in the SA node, which has the capability of originating action potentials and functioning as pacemaker. This action potential then spreads from the SA node throughout the atria and then into and throughout the ventricles.

The contractile cardiac muscle cells don’t normally generate action potentials but they can do in certain pathological conditions. This mean that all parts of the conduction system are able to generate a cardiac impulse; (autorhythmicity), but the normal primary pacemaker is the SA node, while the AV node is a secondary pacemaker and the Purkinje system is a tertiary (or latent) pacemaker. The AV node acts only if the SA node is damaged or blocked, while the tertiary pacemaker takes over only if impulse conduction via the AV node is completely blocked.

The SA node discharges at an intrinsic rhythmical rate of 100-110 times per minute (sinus rhythm). Under abnormal condition; the AV nodal fibers can exhibit rhythmical discharge and contraction at a rate of 40 to 60 times/minute. While those of purkinje fibers discharge at a rate between 15 and 40 times/minute.

Autorhythmicity is a myogenic property independent of cardiac innervation. This is evidenced by the following:

· Completely denervated heart continues beating rhythmically.

· Hearts removed from the body and placed in suitable solutions continue
beating for relatively long periods.

· The transplanted heart (denervated heart) has no nerve supply but they beat regularly.

Self-excitation of SA node:

What causes the SA node to fire spontaneously?

Although the SA node discharges at an intrinsic rhythmical rate of 100-110 times per minute but the pulse rate averages 70 or 80 times per minute, this is because of the effect of vagal tone. SA node does not have a stable resting membrane potential which starts at about – 60 mV. This is due to the inherent leakiness of the SA nodal fibers to Na⁺ions that causes this self-excitation (Na⁺ influx). in other words, because of the high Na⁺ ions concentration in the ECF as well as the negative electrical charge inside the resting sinus nodal fibers, the positive Na⁺ ions outside the fibers tend to leak to the inside, rising the membrane potential up to a threshed to fire an action potential.

Atrioventricular node (AV node):

The conductive system is organized, so that cardiac impulse will not travel from the atria into ventricles too rapidly. There is a delay of transmission of the cardiac impulse in the AV node to allow time for the atria to empty their blood into the ventricles before ventricular contraction begins.

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b) Electrophisiological properties of conduction system.

Action potential of SA node

The resting membrane potential of SA node is of -55 to -60 mV (millivolts). The cause of this reduced negativity “less negative” is that the cell membrane of the sinus fibers are naturally leaky to sodium ions “Na⁺ influx”. Therefore; Na⁺ influx causes a rising membrane potential “gradual depolarization” which when reaches a threshold voltage at about – 40 mV, the fast calcium and sodium channels opened, leading to a rapid entry of both Ca⁺² and Na⁺ions causing the action potential to about 0 mV (zero), to be followed by repolarization which is induced by K⁺ efflux out of the fiber because of the opening of K⁺ channels. This repolarization carries the resting membrane potential down to about -55 to -60 mV at the termination of action potential.

Figure: Action potentials of the SA node.

Action potential of ventricular cardiac muscle fiber

The membrane potential of cardiac ventricular muscle fiber cells is about -90 mV; the interior of the cell is electrically negative with respect to the exterior due to disposition; distribution of ions mainly Na⁺, K⁺ and Ca⁺² ions across its membrane.

The action potential (AP) is an electrical signal or impulse produced by ionic redistribution that the potential changes into positive inside the cell (depolarization), to be followed by restoration of the ions; returning back to the resting potential (repolarization). Stimulation of cardiac muscle cells by SA produces a propagated action potential, that is responsible for muscle contraction i.e., excitation-contraction coupling. In other words, stimulation of cardiac muscle cells specifically those of the ventricles is performed by the propagated AP of the SA node from which the electrical impulses originating and propagated over the heart. According to the figure (a), the propagated AP of the SA node depolarized the ventricular muscle fiber cells rapidly with an overshoot (phase 0), followed by a plateau at around zero potential level (phase 2). This plateau is unique for the heart muscle; and is followed by phase 3 and 4; as final repolarization i.e., for the potential to return to baseline.

Ionic basis of the action potential of the cardiac ventricular muscle fiber cell:

The action potential of cardiac ventricular muscle fiber cell includes the following phases (a):

· Phase 0 (upstroke): initial rapid depolarization with an overshoot to about +20 mV are due to opening of the voltage-gated Na⁺ channels with rapid Na⁺ influx.

· Phase 1 (partial repolarization): initial rapid repolarization is due to K⁺ efflux (K⁺ outflow) followed the closure of Na⁺ channels when the voltage reaches at nearly +20 mV.

· Phase 2 (plateau): subsequent prolonged plateau is due to slower and prolonged opening of the voltage-gated Ca⁺² channels with Ca⁺² influx, Ca⁺² enter through these channels prolong depolarization of the membrane.

· Phase 3 (rapid repolarization): final repolarization is due to opening of the voltage-gated K⁺ channels at zero voltage with rapid K⁺ outflow (K⁺efflux) followed the closure of Ca⁺² channels and, this restores the membrane to its resting potential.

· Phase 4 (complete repolarization): The membrane potential goes back to the resting level (-90 mV) i.e., restoration of the resting potential. This is achieved by the Na⁺-K⁺pump that works to move the excess K⁺ in and the excess Na⁺ out.

Figure (a): The action potential of the ventricular muscle fiber.

Figure: Rhythmical action potentials from a purkinje and ventricular muscle fibers.

Figure: Rhythmical discharge of SA nodal fiber, compared with action potential of ventricular muscle fiber.

c) Function of pacemaker centers.

Some other regions of the heart, including the area around SA-node and the atrio-ventricular bundle can potentially produce pacemaker potentials. The rate of spontaneous depolarization of these cells however is slower, than that of SA-node.

As it determined SA-node produce 60-90 impulses per minute, AV-node – 40-50, bundle of His – 20-30 and Purkinje fibers 10-20 impulses per minute. The potential pacemaker cells are stimulated by action potential from SA-node before they can stimulate themselves through their own pacemaker potentials. If action potentials from the SA-node are prevented from reaching these areas (through blockade of conduction), they will generate pacemaker potentials at their own rate and save as sites for the origin of action as pacemakers.

A pacemaker other than SA-node is called as ectopic pacemaker or ectopic focus.

If the heart of a frog is removed from the body, and put in physiological solution, it will still continue to beat as long as the myocardial cells remained alive.

At a result of experiments with isolated myocardial cells and clinical experience with patients who have specific heart disorders, many regions within the heart have been shown to be capable of originating action potentials and functioning as pacemakers.

In a normal heart, however, only one region demonstrates spontaneous electrical activity and by this means functions as a pacemaker – SA-node.

Conductibility of the heart

a) Conduction of impulses in atria. After excitation of SA-node impulses conduct by bundle of Thorel, Venkenbuh and Buhman to AV-node.

Action potentials from SA-node spread at a rate of 0,8-1,0 m/s across the myocardial cells of both atria. At first the right atrium is excited and left is the second.

b) Peculiarities of conduction through AV-node. The conduction rate slows considerably as the impulse passes into the AV-node. Slow conduction of impulses (0,03-0,05 m/s) through the AV-node is caused by special form of AV-node and peculiarities of impulse development in cells of AV-node, as absence of rapid diffusion of ions. Slow conduction in AV-node is necessary for proper order of contracting atria and ventricles.

c) Excitation of ventricles. After the impulses spread through the AV-node, the conduction rate increases in the atrio-ventricular bundle and reaches 5 m/s in the Purkinje fibers. As a result of this rapid conduction of impulses, ventricular contraction begins 0,1-0,2 s after the contraction of atria.

High velocity of impulses in ventricles is caused by rapid Na⁺-gates.

At first middle part of septum is excited, than impulses spread to apex of heart, than to the right ventricle wall, to the left ventricle wall and to basal parts of ventricles myocardium.

Excitability of heart

a) Excitability changing during excitation. Once contractive myocardial cell has been stimulated by action potentials origin in SA-node, it produces its own action potentials. The majority of myocardial cells have resting membrane potentials of about -90 mV. When stimulated by action potentials from a pacemaker region these cells become depolarized to threshold. At this point their voltage – regulated Na⁺-gates open.

The upshot phase of the action potential of no pacemaker cells is due to the inward diffusion of Na⁺. This period called depolarization.

Following the rapid reversal of the membrane polarity, the membrane potential quickly declines to about -15 mV. Opening K⁺ and Cl^– gates and inward diffusion of K⁺ and Cl^– causes it. This period called quickly initial repolarization.

Then this level potential maintained for 200-300 ms and cells plato phase. It’s due to opening of slow Ca2+ gates. Gradually slow Ca2+ diffusion stops and than diffusion of K⁺ increases. Rapid repolarization at the end of the plato is achieved by rapid outward diffusion of K⁺. During last phase of rest initial distribution of ions inwards and outwards is recovered by function of the sodium-potassium pumps. The heart normally cannot be stimulated until after it has relaxed from its previous contraction because myocardial cells have long refractory periods. It corresponds to the long duration of their action potentials. Summation of contractions is thus prevented and myocardium must relax after each contraction. The rhythmic pumping action of the heart is thus ensured.

Refractory period:

· Absolute refractory period (ARP), it is the interval during which no action potential can be produced, regardless of the stimulus intensity i.e., no stimulus however strong, can produce a propagated action potential. It lasts the upstroke plus plateau and initial repolarization till mid-repolarization at about -50 to -60 mV. It means that the cardiac muscle can not be exited during the whole period of systole and early part of diastole. This period prevents waves summation and tetanus.

· Relative refractory period (RRP), it is the interval during which a second action potential can be produced but at higher stimulus intensity i.e., the heart responds only to stronger stimuli. It lasts from the end of ARP (midrepolarization) and ends shortly before complete repolarization i.e., it lasts for a short period during diastole.

Figure: Relationship between membrane potential changes and contraction in a ventricular muscle cell. The refractory period lasts almost as long as the contraction.

b) Excitability of the heart and skeletal muscles. Electrical impulses that originate at any point of myocardium can spread to all cells, according to ruler “all or nothing”. Because all cells in myocardium are electrically joined a myocardium behaves as a single functional unit. Unlike it, in skeletal muscle contraction depends oumber of excited neurons, which stimulate motor unit. Unlike skeletal muscles, cardiac muscle capable to produce action potentials by pacemaker cells. The rate of heartbeat is regulated by autonomic nervous system. In difference, skeletal muscles are regulated by somatic nervous system.

5. Contractibility of the heart

a) Mechanism of contraction and relaxing of the heart muscle. Like skeletal muscle cells, cardiac muscle cells are striated. They contain actin and myosin filaments arranged in the form of sarcomeres. They contract by means of the sliding filament mechanism. Myocardial cells are short, branched and interconnected. Gap junctions join adjacent myocardial cells. That is why a myocardium contracts to its full extent each time and all of its cells contribute to the contraction. After opening Ca²⁺– gates contraction begins. The mechanism of contraction is similar to skeletal muscles. Sliding on thin filaments they produce shortening of the sarcomeres. In the process of contraction, the thin filaments slide deeper and deeper toward the center, producing increasing amounts of overlap with thick filaments. Sliding of the filaments is produced by the action of numerous cross brigs that extend out from the myosin toward the action. Before the cross brigs combine with actin the globular head function as myosin ATP-ase enzymes. Then cross brigs combine with actin and can attach to actin.

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Mechanism of contraction and relaxing of the heart muscle.

b) Contractibility cardiac and skeletal muscles:

– In skeletal muscles long fibrose cells are separated from each other functionally and structurally. But myocardial cells are short, branched and interconnected by gap junctions.

– Skeletal muscle produce contractions, which are graded depending on the number of cells stimulated. But a myocardium contracts as a single functional unit.

– Skeletal muscles require external stimulation by somatic motor nerves before they can produce action potentials and contract. But cardiac muscle is able to produce action potentials automaticity.

– Skeletal muscle capable to summation of contraction, but myocardial muscle pumps the blood by rhythmic contractions.

Contractility is the ability of the cardiac muscle to contract.

The effect of various factors on contractility is called inotropism; a positive (+ve) inotropic effect means an increase in myocardial contractility, whereas a negative (-ve) inotropic effect means a decrease in myocardial contractility.

Excitation-Contraction coupling in the heart muscle:

As in skeletal muscles, the depolarization wave reaching via the T tubules causes the opening of Ca⁺² channels in the sarcoplasmic reticulum adjacent to the T-tubules. The released Ca⁺² from the cisternae of the sarcoplasmic reticulum (activator Ca⁺²; aCa⁺²) binds to troponin C, leading to cross bridge formation between actin and myosin, which results in contraction.

In cardiac muscle, the amount of this activator Ca⁺² is often insufficient to initiate contraction, but it can be increased indirectly by the following mechanism:

The depolarization wave in the T-tubules opens the long-lasting Ca⁺² channels in the T-tubule membrane, and sarcolemma, Ca⁺² diffuses from the ECF through these channels into the cardiac muscle fibre cell causing a small increase in the cytosolic (fluid of the cytoplasm) calcium concentration in the region of the T-tubules and adjacent sarcoplasmic reticulum. This Ca⁺² is called depolarizing Ca⁺², and although its amount is normally very small, yet it is important because it acts as a signal for the release of large amount of activator Ca⁺² from the cisternae of sarcoplasmic reticulum, it is mainly this cytosolic Ca⁺² that causes the contraction, i.e. once Ca⁺² is in the cytoplasm, it binds to troponin and stimulates contraction. As a result, myocardial cells contract when they are depolarized. The force of contraction is directly proportional to the amount of cytosolic Ca⁺².

Contraction ends when the cytosolic Ca⁺² concentration restored to its original level. In other words, relaxation of the cardiac muscle occurs as a result of release of the actin-myosin combination, this is achieved by decreasing the intracellular Ca⁺² to its pre- contraction level, which occurs by:

1- Active re uptake of Ca⁺² into the sarcoplasmic reticulum by Ca⁺² pump (primary active transport of Ca⁺²).

2- Active pumping of excess Ca⁺² outside the fibres by Na⁺– Ca⁺² exchanger carrier protein (secondary active transport ; counter transport).

The heart normally cannot be stimulated again until after it has relaxed from its previous contraction because myocardial cells have long refractory periods that correspond the long duration of their action potentials. Summation of contractions and tetanus are thus prevented, and the myocardium must relax at each contraction to ensure the rhythmic pumping action of the heart.

Factors that affect cardiac contractility:

· Mechanical

· Cardiac

· Extra cardiac

Mechanical factors:

· Preload (venous return)

· Afterload

The preload:

The preload is the load that determines the initial length of the resting muscle before contraction. The level of the preload is represented by the end-diastolic volume (EDV) i.e., by the venous return (VR). It affects the tension developed in the muscle. When the venous return (EDV), increases, the strength of ventricular contraction increases too, leading to an increase in the stroke volume (Frank-Starling law).

Frank-Starling’s law of the heart

This law describes the length-tension relationship in muscles; it states that the force of contraction of the ventricles depends on the initial length of ventricular muscle fibers. In such a way, that the force of myocardial contraction is directly proportional to the initial length of the cardiac muscle fibres (i.e. to the preload (VR) or EDV). This means that the greater the degree of stretching of the myocardium before contraction, the greater the force of contraction. In other words, Frank-Starling law reflects the relationship between ventricular end-diastolic volume (EDV) and stroke volume; when the blood returns to the heart during the filling phase, this blood will distend the ventricles so the ventricles will produce more powerful contraction to pump the increased volume of the blood.

The Significance of Frank-Starling’s law

The Starling’s law allows autoregulation of myocardial contractility (regulation of the contractility by changing the length of the muscle fibers), in the following conditions:

(1) Iormal hearts. Starling’s law allows changes in the right ventricular
output to match changes in the venous return (VR), and maintains equal
outputs from both ventricles. For example, if the systemic VR increases,
the EDV of the right ventricle increases, leading to a forceful contraction
that increases its output to match the increased VR. At the same time, the
increased right ventricular output increases the pulmonary VR to the left
ventricle, which also increases its EDV, resulting in an increase of its output, which balances the increased right ventricular output.

(2) In denervated hearts (e.g. transplanted hearts); autoregulation of myocardial contractility becomes the main mechanism.

(3) In cases of rise of the arterial blood pressure: the stroke volume of the left ventricle would decrease. However, the retained blood in the left ventricle plus blood returning to it from the left atrium during the next diastole increase the EDV. This leads to a forceful contraction, thus the accumulated blood in the left ventricle will be ejected in spite of the increased arterial blood pressure.

The Afterload:

The afterload is the load that the muscle faces when it begins to contract. In the intact heart, the afterload is produced by the aortic impedance which is determined by:

· The aortic pressure (arterial systolic blood pressure).

· The arterial wall rigidity (arteriosclerosis).

· Blood viscosity (polycythemia).

Cardiac factors:

· The myocardial mass.

· The heart rate.

The myocardial mass:

A significant injury or loss of the functioning ventricular muscle (e.g. due to ischemia or necrosis) decreases the force of myocardial contractility. This also occurs in cases of heart failure.

The heart rate:

The force of cardiac contractility is affected by the frequency of stimulation. An increase in the frequency of stimulation (i.e. shortening the intervals between the stimuli) causes a proportional increase in the force of contraction.

Accordingly, tachycardia causes a +ve inotropic effect while bradycardia exerts a -ve inotropic action. The +ve inotropic effect in tachycardia is due to the increase in the number of depolarization (which increases the intracellular Ca⁺² content and its availability to the contractile proteins (troponin C)).

Extra cardiac factors:

These factors affect the cardiac inotropic state and they include the following:

· Neural

· Physical

· Chemical

Neural factors:

Sympathetic stimulation and noradrenaline exert a +ve inotropic effect by increasing;

· Cyclic-AMP in the cardiac muscle fibres (which leads to activation of the Ca⁺² channels and more Ca⁺² influx from the ECF).

· The heart rate.

Conversely, parasympathetic stimulation and acetylcholine exert a -ve inotropic effect (by opposite mechanism) but on the atrial muscle only (since the vagi nerves don’t supply the ventricles).

Physical factors:

A moderate rise of the body temperature strengthens cardiac contractility (by increasing the Ca⁺² influx and ATP formation in the muscle) while an excessive rise of the body temperature (e.g. in fever) exhausts the metabolic substrates in the cardiac muscle and decreases its contractility. Hypothermia also decreases cardiac contractility.

Chemical factors:

(A) Hormones:

Catecholamines (epinephrine, norepinephrine and dopamine), glucagon and the thyroid hormones; all exert a +ve inotropic effect.

(B) Blood gases:

Moderate hypoxia (O₂ lack) and hypercapnia (CO₂ excess) increase the cardiac contractility, whereas severe hypoxia and hypercapnia directly depress the cardiac muscle and decrease its contractility.

An increase of the blood [H⁺] i.e. drop of the blood pH (acidosis) produces a -ve inotropic effect, whereas a decrease of the blood [H⁺] i.e. rise of the blood pH (alkalosis) produces a + ve inotropic effect.

(D) Inorganic ions:

· Sodium: Hypernatraemia favors Na⁺ influx and Ca⁺²efflux by the
Na⁺-Ca⁺² exchanger carrier, thus it has a -ve inotropic effect. On the other
hand, hyponatraemia exerts a +ve inotropic effect by an opposite mechanism.

· Potassium: Hyperkalaemia has a -ve inotropic effect (weakens the myocardial contractility; flaccidity) and may stop the heart in diastole. This is because the excess K⁺ in the ECF decreases the resting membrane potential (more positive resting membrane potential; closer to the threshold)) in the cardiac muscle fibers, so the amplitude of the action potential is reduced leading to less influx of the depolarizing Ca⁺² and in turn less release of activator Ca⁺² from the sarcoplasmic reticulum. In addition, Hyperkalaemia increases excitation and decreases conduction leading to ectopics and dilated, flaccid heart. On the other hand, hypokalaemia produces a +ve inotropic effect by an opposite mechanism.

· Calcium: Hypercalcaemia exerts a +ve inotropic effect as a result of more cytosolic Ca⁺². Whereas hypocalcaemia has a little (or no) -ve inotropic effect, since lowering of the serum Ca⁺² level causes fatal tetany before affecting the heart. However, hypocalcaemia causes cardiac flaccidity like Hyperkalaemia.

(E) Toxins:

Several toxins (e.g. certain snake venoms and the toxin released by the diphtheria microorganisms) produce a-ve inotropic effect (mostly by a direct action on the contractile mechanism of the cardiac muscle).

(F) Drugs:

· Cardiac glycosides (e.g. digitalis; Digoxin): These drugs inhibit the Na⁺-K⁺ ATPase in the sarcolemma of the cardiac muscle fibres, so the intracellular Na⁺ concentration increases. This decrease the Na⁺ influx, thus Ca⁺² efflux through the Na⁺-Ca⁺² exchanger is also decreased. Accordingly, the intracellular Ca⁺² concentration increases, producing a +ve inotropic effect. Digitalis also increases the slow Ca⁺² influx during the action potential.

· Xanthines (e.g., caffeine and theophylline; bronchodilator): They exert a +ve inotropic effect.

· Ouinidine, barbiturates, procainamide (and other anesthetic drugs) as well as Ca⁺² blocker drugs all have a -ve inotropic effect by decreasing Ca⁺² influx into the cardiac muscle fibres.

Separate myocardial cell electricity.

Potential changes on cell membrane, which is recorded separately called electro gram. During resting potential membrane charge is positive. If two electrodes will dispose on membrane surface the voltage difference is absent and baseline is recorded. In irritation the cell membrane is depolarized some part firstly. The voltage between two electrodes increased and electro gram line deflects upward. The positive wave of electro gram is formed. After depolarizing all the membrane its surface charge becomes negative. The voltage under both electrodes temporarily becomes the same. Electro gram line returns downward to baseline level. Then repolarization begins from the same point as depolarization and in the same order. Polarity of cell membrane changes and electro gram deflects downward. The negative wave is formed. After depolarization of hole the membrane surface the voltage returns to rest potential level and baseline on electro gram record.

Electrogram and action potential of one myocardial cell.

During the depolarization phase the rapid Na⁺ gates open and inward diffusion of Na⁺ occur. This event corresponds to formation upward part of positive wave on electro gram line. The next fast initial repolarization begins with inward Cl^– diffusion. Then electro gram returns to baseline level. When opening slow Ca²⁺ gates the potential difference temporarily isn’t essential and baseline continues. During the next phase outward K+ diffusion increases and external surface of membrane becomes positive. Voltage fluctuation leads to deflection of electro gram downward further returning to baseline level. In rest period all the membrane has positive charge on external surface and baseline is recorded. Through this period ion pumps restore initial distribution of ions.

Formation of Electro gram waves

An electrocardiograph is an instrument that measures and records the electrocardiogram (ECG), the electrical activity generated by the heart. Electrodes placed on various anatomical sites on the body help conduct the ECG to the electrocardiograph. The ECG alone is not sufficient to diagnose all abnormalities possible in the pacing or conduction system of the heart. The interpretation of the 12-lead ECG provides a differential diagnosis for many arrhythmias.

The electrical current generated by the heart is conducted through the pairs of electrodes and leads, and is amplified, recorded, and processed by the electrocardiograph. The wires connecting the pairs of electrodes on the surface of the body to the electrocardiograph are called leads. The different features and modules of a typical electrocardiograph include the protection circuitry, lead selector, calibration signal, preamplifier, isolation circuit, driver amplifier, memory system, microcomputer, and recorder or printer.7

Twelve leads usually comprise a diagnostic ECG recording: six limb leads (three bipolar and three unipolar), and six unipolar precordial leads. The instantaneous cardiac scalar voltages resulting from the electrical activity in the heart is measured in each of the 12 leads. Since the cardiac vector varies in magnitude with time over a three-dimensional space, it is important to know its presentation (i.e. appearance or projection) in each of the 12 leads of the ECG.

Figure 4.1 shows the lead placement to acquire the 12-lead ECG. The leads can be categorized into the frontal leads (I, II, III, aVR, aVL, and aVF), and the transverse leads (V1, V2, V3, V4, V5, and V6). The frontal leads measure the projection of the cardiac vector on the frontal plane of the body. The frontal plane is parallel to the floor when lying supine. The transverse or precordial leads measure the projection of the cardiac vector on the horizontal plane, (i.e. the plane that is parallel to the floor when standing).

Leads I, II, and III of the frontal plane are bipolar. They record the differences between two points on the body. Figure below shows that lead I is measured between an electrode on the left arm (the positive electrode) and an electrode on the right arm. The three-dimensional cardiac vector projects into each of the bipolar leads, indicating the strength and direction of the instantaneous cardiac vector.

Figure The instantaneous cardiac vector projects into each of the leads, resulting in different morphologies. ECG sketches are that of a normal morphology.

Leads aVR (on the right arm), aVL (on the left arm), and aVF (on the foot) are unipolar leads. They measure the potential difference on the limbs with respect to a reference point formed by the two resistors between limb electrodes (Figure 4.1). For example, lead aVR is measured between an electrode on the right arm, and a reference point formed via a resistor to the left arm and another resistor to the left foot. These leads show the cardiac vector projection on the frontal plane, and are amplified by about 50% (i.e. augmented) so that their amplitudes are comparable to those of the bipolar leads.

The six precordial leads, V1 to V6, are unipolar and measure the cardiac vector projection on the horizontal plane. These precordial leads are measured with respect to the Wilson central terminal which is formed by a three resistor network as shown in Figure 4.1. V1 and V2 are placed on the fourth intercostal space to the right and left, respectively, of the sternum. The V4 electrode is placed on the fifth intercostal space at the left midclavicular line. The V3 electrode lies between V2 and V4. Electrode V5 is placed to the left of V4 on the anterior axillary line, and V6 is placed on the same level as V5 on the midaxillary line. It is important to account for the position of these electrodes when interpreting the ECG on leads V1 through V6. The precordial leads measure the potential between each of V1 through V6 and the Wilson’s central terminal formed as shown in Figure 4.1.

The 12-lead ECG provides various viewpoints of the three-dimensional instantaneous cardiac vector that are somewhat redundant, and this is helpful in providing discriminatory information for diagnosing abnormalities in the pacing and conduction system of the heart.

The electrical activity due to the specialized cells in the heart results in an electric potential on the surface of the body. Each cell can be modeled by a dipole, and the superposition of the potentials from the dipoles for all of the cells in the myocardium results in a three-dimensional cardiac vector for the heart at each instant in time. The cardiac vector at each instant of time represents the net electrical activity in the heart.

Figure The Hexaxial system shows the orientation of the frontal plane leads. During left axis deviation (LAD), the mean axis of the QRS will be less than –30°. RAD: right axis deviation.

Figure on the left shows the Hexaxial reference system which is used in the diagnosis of certain abnormalities. The Hexaxial system shows the orientation of the frontal-plane leads. The various orientations of each lead result in a different projection of the cardiac vector onto that particular lead. A mean electrical axis as a function of time, during the depolarization and repolarization phases of a cardiac cycle can be calculated. For example, the electrical axis of ventricular depolarization, ÂQRS, represents the average of the instantaneous cardiac vectors during ventricular depolarization. The ÂQRS, usually lies between aVL and aVF in Figure 4.2. It is easy to diagnose left and right axis deviation, LAD and RAD respectively. In LAD, lead I is predominantly positive (i.e. R wave is positive) and both leads II and III are predominantly negative (i.e. R wave is small or absent). Both II and III must be predominantly negative, i.e. if in lead II the S wave is smaller than the R wave, LAD is not present. If lead II is equiphasic (R and S waves have equal magnitudes), then there is borderline LAD. In RAD, lead I is predominantly negative and both II and III are predominantly positive (Bennett, 1989).

Figure below shows the Einthoven triangle superimposed on the locus of points formed in the frontal plane by a normal instantaneous cardiac vector, the vectorcardiographic loop during one cardiac cycle. The measured ECG on each lead is a projection of the instantaneous cardiac vector. The P loop corresponding to atrial contraction, projects onto leads I, II, and III as an upward deflected wave. However, the S wave is projected onto lead III remarkably more than in leads I and II. The instantaneous orientation of the cardiac vector, and the orientation of the lead determine whether there is a positive going or negative going waveform on the lead. Thus the different leads of the 12-lead ECG show various projections of the phases in the cardiac cycle.

Figure For a normal ECG, the instantaneous cardiac vector projects into lead III with a more negative S wave than in lead I. The dashed line indicates how the QRS complex projects onto lead I. Shaded areas represent key segments of the ECG.

ECG correspondence of heart depolarization

Every cardiac cycle produces ECG waves designated as P, Q, R, S and T. These waves are not action potentials. They represent potentials between rested and depolarized or depolarized and repolarized parts of whole heart. Amplitude and duration of these waves correspond to electrical power fluctuation in entire heart.

After producing impulse in SA-node depolarization begins at first in cells of right atrium and ascend part of P wave is recorded. When depolarization spreads into left atrium, the ECG line returns to baseline level. Delay of depolarization in AV-node recorded as PQ-interval in baseline. Then impulse spreads into middle part of septum and heart apex. This event recorded as descend part of Q wave. Iext depolarization of right ventricle wall ECG line deflexed upward and formation of R wave begins. When impulse spreads into left ventricle wall, the ECG line returned in contrary side towards the lowest point of S wave. Depolarization of ventricles basis afterwards caused formation of S wave, which continues to baseline.

Repolarization of atria is failed to record in ECG because of greater depolarization of ventricles. Repolarization of ventricles develops firstly in right part of heart and then in left one. That is why ascend and descend parts of T wave are formed.

In diastole normally baseline is recorded but U wave may occur.

ECG leads

a) Bipolar limb leads. The bipolar limb leads record the voltage between electrodes placed on the wrists and legs. These leads were proposed by Einthoven in 1913.

I lead: left arm (+) – right arm (-);

II lead: left leg (+) – right arm (-);

III lead: left arm (+) – left leg (-).

For recording limb leads we put red electrode on right arm, yellow – on left arm, green – on left leg and black – on right leg. Black electrode has zero potential (ground).

b) The unipolar limb leads were proposed by Goldberger in 1942. They record voltage between single “exploratory electrode” fro one limb and zero joined electrode from two other limbs. So there are three leads AVR, AVL, AVF. In fact zero electrodes records middle voltage of two limbs. Bipolar limb leads and unipolar limb leads record electrical power in frontal projection.

c) The unipolar chest leads were suggested in 1934 by Vilson. One electrode, which is active, situated on the chest in six standard positions. They labeled V1 – V6. Joined zero electrode records middle potential of right arm, left arm and left leg. That is why every chest lead records voltage between active chest electrode and Vilson’s joined zero electrode.

These standard positions of active chest electrode are:

V1 – in crossing right IV right intercostal space and parasternal line;

V2 – in crossing left IV intercostal space and parasternal line;

V3 – between V2 and V4;

V4 – in crossing V left intercostal space and medioclavicular line;

V5 – in crossing V left intercostal space and anterior axilar line;

V6 – in crossing V left intercostal space and middle axilar line.

Unipolar chest leads records changes of heart polarity in horizontal projection.

Algorithm of ECG registration

Registration performs fare from electric motors and other electrical devices.

Tested person may have rest before registration in 10-15 minutes. This procedure needs 2-hour interval after eating or worm procedures.

For better contact between electrodes and skin use solution NaCl 5-10 % or special electrode past or electrode gel. Otherwise hindrances in ECG curve may occur. They will stand in the way of ECG analysis

ECG registration performs in quiet breathing in patients.

Registration begins from standard voltage 1 mV from the electrocardiograph for regulation of amplitude in ECG. Usually standard voltage amplitude is 10 mm. Then continue registration of bipolar limb leads, the next – unipolar limb leads and afterwards – unipolar chest leads.

Characteristics of a normal ECG

In order to interpret the 12-lead ECG and use it to diagnose abnormalities, it is important to know the normal characteristics of the ECG, and understand the mechanisms underlying the generation of each segment of the ECG. Figure 4.4 shows the various fiducial points in the ECG, and typical values of the various intervals measured from the ECG.

The P wave is caused by atrial depolarization. The duration is normally not greater than 110 ms. The normal shape of the P wave does not include any notches or peaks. It is normally positive in leads I, II, aVF, V4 to V6. It is normally negative in aVR. It can be positive, negative, or diphasic in the remaining leads. If it is diphasic, then the negative component comes after the positive component and is not excessively broad or deep. An absent P wave in the ECG may signify sinoatrial block, an abnormality in which the impulse from the SA node is not conducted to the AV node.

The QRS complex is a general term representing activation in the ventricles and is a result of the depolarization of the ventricles. The duration is normally less than 100 ms. The Q and S waves represent negative (downward) deflections on the plot of the lead, and the R wave represents positive (upward) deflections. The Q wave comes before the R wave, and the R wave comes before the S wave. Not all of the Q, R, and S components have to be present on any particular lead. The actual QRS morphology is specified using the letters, q, Q, r, R, s, and S. An upper case letter signifies a bigger size of the wave than the corresponding lower case letter. For example, a QRS morphology consisting of a small downward deflection, followed by a large upward deflection, and then a small downward deflection would be labeled as qRs. Normally, the initial portion of the QRS complex is a narrow q wave in leads I, V6, and aVL, and a narrow r in lead V1 which may sometimes be absent. The end portion of the QRS normally has an S wave in V1, and an R wave in V6 (i.e. no downward deflection after R wave in V6). A QRS complex duration of more than 120 ms can reflect an abnormality due to intraventricular conduction.

The T wave results from ventricular repolarization. The normal morphology of the T wave is rounded and asymmetrical. In the normal ECG it is positive in leads I, II, V3, to V6, and negative in lead aVR. The polarity may vary in leads III, V1 and V2. The polarity is positive in aVL and aVF, but it may be negative if QRS has a small amplitude.

The S–T segment is measured from the end of QRS complex (J point) to the onset of the T wave. This segment represents the early stage of ventricular repolarization and under normal conditions is isoelectric (constant potential). It may be slightly elevated in leads I, II, III, and the precordial leads. It is normally not depressed in any lead. A marked displacement of the S–T segment signifies coronary artery disease (e.g. a marked elevation could suggest myocardial infarction).

The P–R interval represents the atrioventricular (AV) conduction time, i.e. the time required for the electrical impulse to propagate from the sinus node through the atrium and the AV node to the ventricles (which results in ventricular depolarization). The normal range of the P–R interval is 120 ms to 200 ms. This interval can vary with heart rate.

The Q–T interval reflects the total duration of ventricular systole, and is measured from the onset of the QRS complex to the end of the T wave. Normally the Q–T interval is less than half the preceding R–R interval. Q–T lengthening may be caused by bradycardia or hypothermia.

The U wave, which is not always recorded on the ECG, follows the T wave and usually has the same polarity as the T wave. It is recorded best in leads V3 and V4. It becomes more evident with hypokalemia, bradycardia, and age.

ECG analysis begins with estimation of control voltage and paper speed. Another analysis at usual performs in this order.

1) Determining of impulse origin. Pay attention to proper order of waves in ECG. If P wave in II lead is positive and recorded before QRS complex is believed to determine pacemaker in SA node.

2) Heart rhythm evaluation by measuring of R-R duration. Normally adjacent R-R intervals duration may differ from each other not more 0.1 s. Usually II lead is examined.

3) Determining of heart rate. In proper rhythm 60 s is divided to R-R duration in seconds, which is calculated using paper speed.

4) Evaluation of ECG voltage. If in bipolar limb leads the lowest R wave is smaller than 5 mm and RI+RII+RIII less than 15 mm, the ECG voltage is decreased. Otherwise it is normal.

5) EMP direction determining.

– Visual method: needs measuring R amplitude in all bipolar limb leads. If true, that R_II>R_I>R_III, the EMP direction is near 30º-69º, that is normal;

– Graphic method use Baily co-ordinate. If in Einthoven’s triangle put through the center parallel to leads axes we’ll get Baily’s co-ordinate. Than in any two bipolar limbs leads it is necessary to determine summary amplitude of QRS waves. Upward waves have positive meaning and downward are negative. Summary amplitude put on corresponding axis with (+) or (-) sign. In this point lined perpendicular to lead axis. Next time determined cross point of two drown perpendiculars. When join this point to Baily’s co-ordinate center we’ll obtain the EMP direction outward the center.

6) ECG elements analysis. Pay attention to form, amplitude and duration of waves and intervals. Measure deviation from baseline if it occurs. Compare the results with normal rate.

Amplitudes of waves at norm in adults in mm (1 mv =10 mm)

Waves

Leads

ІІ

ІІІ

aVR

aVL

aVF

0,1-1,3

0,3-2,5

0,5-2,0

1,0-(-0,1)

-0,5-0,8

-0,3-1,5

0,8-1,6

0,2-2,6

0-1,8

0,1-2,3

0-2,4

0-1,4

Less than 25 % of wave R amplitude

0-4

0-6

0-8

0-3,5

0-3

0-0,5

0-1,6

0-2,1

0-2,7

1-12

2-17

0,5-13

0-5

0-10

0-20

0-7

0-16

1,5-26

4,0-27

4-26

4-22

0-3,5

0-5,0

0-5,5

0-13

0-18

0-8

2-25

0-29

0-25

0-20

0-6

0-7

S-T

-0,5-1

0-2

-0,5-1

1-5

1-6,5

-1,-3,5

-5-1,5

-4-6

-0,5-5

-4-4

-3-18

-2-16

0-17

0-9

-0,5-5

The main elements of ECG curve are:

– Waves P, Q, R, S and T. Sometimes U wave may occur;

– Segments – P-Q (from the end of P wave to beginning of Q wave), S-T (from the end of S wave until beginning of T wave);

– Intervals, which characterize certain time period of heart activity – P-Q (from the beginning of P wave to beginning of Q wave), Q-T (from beginning of Q wave to end of T wave);

– Complexes – atrial, which is presented by P wave, and ventricular -QRST.

a) P wave in healthy persons, is obligatory positive in I, II, AVF, V₂-V₆ leads. P wave may be negative in III, AVL and V1, either positive or biphasic. Normally in II lead its amplitude is 2.5 mm, duration – 0.1 s.

b) P-Q interval reflects duration of AV-conduction, which is spreading of potential by AV node, His bundle and its branches. This interval lasts 0.12-0.20 s and depends on heartbeat rate.

c) QRST complex reflects spreading of excitation by ventricles. It hole amplitude is higher 5 mm of the waves are signed by capital letters. Otherwise it used little letters. ORS duration in II lead is not more than 0.1 s.

d) Q wave normally in II lead is less then 1/4 of R amplitude duration is 0.03 s. Normally in AVR deep and wide Q waves may be recorded. In V₁, V₂ – Q wave is particularly absent.

e) R-view usually is recorded in all leads; exalt AVR, which may be absent. In unipolar chest leads R amplitude gradually increases from V₁ to V₄ and some decreases in V5 and V6. So normally in unipolar chest leads both increasing R-amplitude and S-amplitude occurs. S-wave has amplitude not more than 20 mm, but it varies from lead to lead.

j) S-T –segment corresponds to excitation of both ventricles. Normally in bipolar and unipolar leads it lies on baseline and don’t move more than 0.5 mm. In V1-V3 deviation upward to 2 mm may occur.

h) T-wave normally is positive in I, II AVF, V₂-V₆, T_I>T_III, T_V6>T_V1. T-wave has sloping ascend part and sleep descending part. In III, AVL, V₁ T-wave may either be positive, negative or bipolar. In II lead T-amplitude is 5-6 mm, duration – 0.16-0.24 s.

i) Q-T interval is electrical systole of ventricles. Its duration directly depends on heartbeat rate. Proper duration may calculated by Buzett formula:

Q-T=K√¯R-R¯, where

K=0.37 in male or 0,40 in female

f) U-wave may be recorded in unipolar chest leads, which reflects excitation fare of excitability after electrical systole of ventricles myocardium. U-wave usually is positive and small.

Ambulatory ECG monitoring

Ambulatory monitoring is a noninvasive technique used for correlating between a patient’s symptoms and the presence of arrhythmias, evaluating an antiarrhythmic drug therapy, classifying risk in postmyocardial infarction patients, and monitoring pacemaker function such as recording heart rate with different activities (Luna, 1993). Since the occurrence of abnormal cardiac electrical behavior may occur sporadically or in response to certain stimuli, it is important to record the ECG over long periods of time.

Holter recording is a technique for acquiring a continuous ECG. Magnetic tape, and more recently solid-state memory is used to store recordings of the ECG. In the former technique the signal is stored on tape in analog form (frequency-modulated systems are also used), and in the latter case digital compression algorithms may be used to store long-term digital data on a limited memory bank. Modern Holter systems provide sophisticated static RAM technology which can store data recorded over many days. Two ECG leads are often used to ensure an accurate interpretation of the ECG. The recorder is small, lightweight, and acceptable for the patient to wear. Holter monitors can acquire and process the ECG in real time. Current ambulatory monitors can make recordings for several days.

Analysis of the 24‑h tape requires 30 to 60 min to obtain information of arrhythmias and S–T‑segment changes. A report of a compressed version of the ECG is usually available for the clinician to validate the automated results given by the monitor. Modern scanners include features to provide a tabulated summary of relevant data, and record and analyze the Q–T interval variability over a long period. The variability of the Q–T interval in postmyocardial infarction patients can be useful to stratify risk of malignant ventricular arrhythmias.

Holter recording is useful for patients who have transient symptoms which suggest a cardiac abnormality. Many patients with a variety of symptoms such as palpitations, dizziness or syncope (transient loss of consciousness), a previous ischemic stroke, and chest pain are diagnosed with Holter recordings. Holter recordings are used to correlate the patient’s symptoms with the presence of arrhythmias. Patients wearing Holter monitors usually keep a record of activities and times when their symptoms occur, so that the activities may be correlated with the ECG recording.

Holter monitoring provides a method to document the electrophysiologic mechanisms of arrhythmias. A study of 200 Holter monitor tapes of patients who died while being monitored, i.e. an arrhythmia resulted in sudden death. Ventricular tachycardia was the cause of sudden death in 80% of the cases, and bradycardia accounted for the remaining 20% of the cases. Holter monitoring is also used to document pacemaker function and record changes in heart rate with different activities. It can also be useful to detect any malfunctions in the pacemaker pacing or sensing functions. Current ambulatory monitors include a separate channel for recording the pacing stimulus, and can automatically provide information concerning failure to capture, failure to sense, failure to generate an impulse, and percent of beats paced. Even though these features are currently reliable for single-chamber pacemakers, additional work needs to be done for the automatic evaluation of dual-chamber pacemakers analysis.

Exercise stress testing

Exercise stress testing is used to evaluate the cardiovascular response (changes in blood pressure, heart rate, and O2 consumption) to exercise. It is useful in the diagnosis and evaluation of ischemic heart disease, and the assessment of cardiac arrhythmias.

The heart extracts 70% of the oxygen carried by the blood flowing through the myocardium. During exercise, an increase in myocardial oxygen demand must be matched by an increase in coronary blood flow, otherwise ischemia will result. In the presence of ischemic heart disease (IHD), coronary blood flow cannot increase adequately to meet the demands of the myocardium for O2. This results in ischemia and may be manifested by pain (angina), changes in the ECG S–T segment, ventricular dysfunction, or arrhythmias.

Exercise capacity is described using the “double product,” the product of heart rate and blood pressure. The exercise testing methodology is designed to produce an increase in heart rate to 85% to 90% of the statistical maximum for the patient’s age and sex. The exercise testing is carried out in a suitable temperature, in an environment equipped for cardiorespiratory emergencies. A bicycle or treadmill is used, and the Bruce or Ellestad protocols are the ones most widely used. The exercise protocols involve multiple stages of increments in intensity of exercise, over minimal intervals of three minutes. Patients are monitored for symptoms such as precordial pain, and hemodynamic changes. The 12-lead ECG is acquired with the patient supine, and standing prior to the test, during each step in the exercise protocol, immediately following the exercise, and at 2-min intervals after the exercise for 10.

S–T segment changes are the most reliable ECG diagnostic criteria of myocardial ischemia. S–T segment changes during the exercise test is due to an intracellular potassium loss resulting from an imbalance between the myocardial O2 supply and demand. The S–T segment changes can be isoelectric, junctional (near the J point of the ECG), a horizontal depression, down-sloping, slow rising, or elevated. A marked horizontal or down-sloping S–T segment below the isoelectric line and which persists for 80 ms is interpreted as a positive test. The depth of the S–T segment depression correlates roughly with the extent of the coronary artery disease. The interpretation of the exercise test should take into account the workload of the exercise, the heart rate and blood pressure response, and the presence or absence of arrhythmias or symptoms. False positive and false negative results are possible during situations of left bundle branch block, left ventricular hypertrophy, Wolff–Parkinson–White syndrome, and changes due to digitalis.

Cardiac Physiology – Anatomy Review

Functions of the Heart

Generating blood pressure

Routing blood

Heart separates pulmonary and systemic circulations

Ensuring one-way blood flow

Regulating blood supply

Changes in contraction rate and force match blood delivery to changing metabolic needs

Blood Flow Through and Pump Action of the Heart

Blood Flow Through Heart

Cardiac Muscle Cells

Myocardial Autorhythmic Cells

Membrane potential “never rests” pacemaker potential.

Myocardial Contractile Cells

Have a different looking action potential due to calcium channels.

Cardiac cell histology

Intercalated discs allow branching of the myocardium

Gap Junctions (instead of synapses) fast Cell to cell signals

Many mitochondria

Large T tubes

Electrical Activity of Heart

Heart beats rhythmically as result of action potentials it generates by itself (autorhythmicity)

Two specialized types of cardiac muscle cells

Contractile cells

99% of cardiac muscle cells

Do mechanical work of pumping

Normally do not initiate own action potentials

Autorhythmic cells

Do not contract

Specialized for initiating and conducting action potentials responsible for contraction of working cells

Intrinsic Cardiac Conduction System

SA Node 70-80 bpm

Sets the pace of the heartbeat

AV Node 40-60 bpm

Delays the transmission of action potentials

Purkinje fibers 20-30 bpm

Can act as pacemakers under some conditions

Intrinsic Conduction System

Autorhythmic cells:

Initiate action potentials

Have “drifting” resting potentials called pacemaker potentials

Pacemaker potential – membrane slowly depolarizes “drifts” to threshold, initiates action potential, membrane repolarizes to -60 mV.

Use calcium influx (rather than sodium) for rising phase of the action potential

Pacemaker Potential

K+ channels closed: Decreased efflux of K⁺

Constant influx of Na⁺: no voltage-gated Na⁺ channels

Drifting depolarization: K⁺ builds up and Na⁺ flows inward

Voltage-gated Ca²⁺ T-channels open at ~ -55mV: Small influx of Ca²⁺ further depolarizes to threshold (-40 mV) via “Transient Channels”

Voltage-gated Ca²⁺ L-channels open at Threshold: sharp depolarization due to activation of Ca²⁺ L channels allow large influx of Ca²⁺ via “Long Lasting Channels”

Peak at ~ +20 mV: Ca-L channels close, voltage-gated K channels open, repolarization due to normal K+ efflux

K+ channels close: at -60mV

AP of Contractile Cardiac cells

Contractile cells

Rapid depolarization

Rapid, partial early repolarization, prolonged period of slow repolarization which is plateau phase

Rapid final repolarization phase

Action potentials of cardiac contractile cells exhibit prolonged positive phase (plateau) accompanied by prolonged period of contraction

Ensures adequate ejection time

Plateau primarily due to activation of slow L-type Ca²⁺ channels

Why A Longer AP In Cardiac Contractile Fibers?

At no time would we want summation and tetanus in our myocardium

Because long refractory period occurs in conjunction with prolonged plateau phase, summation and tetanus of cardiac muscle are impossible

Plateau ensures alternate periods of contraction and relaxation which are essential for pumping blood

Refractory period

Membrane Potentials in Autorhythmic and Contractile cells

Action Potentials

Excitation-Contraction Coupling in Cardiac Contractile Cells

Action potential from Autorhythmic cells is passed to contractile cells, propagating down T-tubules, causing a small influx of Ca²⁺ via Ca²⁺ L-channels

Ca²⁺ entry through L-type channels in T tubules triggers larger release of Ca²⁺ from sarcoplasmic reticulum

Ca²⁺ induced Ca²⁺ release leads to cross-bridge cycling and contraction

Electrical Signal Flow – Conduction Pathway

Cardiac impulse originates at SA node

Action potential spreads throughout right and left atria

Impulse passes from atria into ventricles through AV node (only point of electrical contact between chambers)

Action potential briefly delayed at AV node (ensures atrial contraction precedes ventricular contraction to allow complete ventricular filling)

Impulse travels rapidly down interventricular septum by means of bundle of His

Impulse rapidly disperses throughout myocardium by means of Purkinje fibers

Rest of ventricular cells activated by cell-to-cell spread of impulse through gap junctions

The heart

The heart is a muscular organ enclosed in a fibrous sac (the pericardium).The pericardial sac contains watery fluid that acts as a lubricant as the heart moves within the sac. The wall of the heart is composed of cardiac muscle cells, termed the myocardium. The inner surface of the wall is lined by a thin layer of endothelial cell; the endothelium. The heart is actually two separate pumps; a right heart which pumps blood through the pulmonary artery into the lung, and a left heart which pumps blood through the aorta into the peripheral organ. Each of these two pumps is consists of two chambers, an atrium and a ventricle, separated by atrioventricular valve (left; mitral valve and right; tricuspid valve). Blood exists from the right ventricle through the pulmonary valve to the pulmonary trunk, and from the left ventricle through the aortic valve into the aorta.

Pulmonary and Systemic Circulations

Blood whose oxygen content has become partially depleted and carbon dioxide content has increased as a result of tissue metabolism returns to the right atrium. This blood then enters the ventricle, which pumps it into the pulmonary trunk and pulmonary arteries. The pulmonary arteries branch to transport blood to the lungs, where gas exchange occurs between the lung capillaries and the alveoli of the lungs. Oxygen diffuses from the air to the capillary blood; while carbon dioxide diffuses in the opposite direction. The blood that returns to the left atrium by way of the pulmonary veins is therefore enriched in oxygen and partially depleted of carbon dioxide. The blood that is ejected from the right ventricle to the lungs and back to the left atrium completes one circuit: called the pulmonary circulation.

Oxygen-rich blood in the left atrium enters the left ventricle and is pumped into a very large, elastic artery; the aorta. The aorta ascends for a short distance, makes a U-turn, and then descends through the thoracic and abdominal cavities. Arterial branches from the aorta supply oxygen-rich blood to all of the organ systems and are thus part of the systemic circulation. As a result of cellular respiration, the oxygen concentration is lower and the carbon dioxide concentration is higher in the tissues than in the capillary blood. Blood that drains into the systemic veins is thus partially depleted of oxygen and increased in carbon dioxide content. These veins empty into two large veins; the superior and inferior venae cavae that return the oxygen-poor blood to the right atrium. This completes the systemic circulation; from the heart (left ventricle), through the organ systems, and back to the heart (right atrium).

Physiology of cardiac muscle

The heart is composed of three major types of cardiac muscle.

1- The atrial muscle.

2- The ventricular muscle.

3- Specialized excitatory and conductive muscle fibers; an excitatory system of the heart that helps spread of the impulse (action potential) rapidly throughout the heart.

Physiologic anatomy of cardiac muscle

Cardiac muscle cells (myocytes) are striated as they have typical myofibrils containing thin actin and thick myosin filaments, similar to those found in skeletal muscle, which slide along each other during the process of contraction.

Unlike skeletal muscle (no gap junction), adjacent myocardial cells are joined end to end at structures called intercalated discs, which are cell membranes that have very low electrical resistance. Within the intercalated discs, there are electrical synapses or gap junctions, these gap junctions are protein channels that allow ions to flow from the cytoplasm of one cell directly into the next cell and, therefore action potentials to move with ease from one cardiac myocyte to another. That is, when one of these cells becomes excited, the action potential spreads rapidly throughout the intercalated discs and gap junctions to stimulate the neighbor cell, so the myocardium act almost as if it is a single cell; a syncytium, i.e., the cardiac muscle contracts or behaves as a single functional unit (syncytium property).

Innervations of the heart

The heart receives a rich supply of sympathetic and parasympathetic nerve fibers. The parasympathetic contained in the vagus nerves release acetylcholine which acts on the muscarinic receptors. The sympathetic postganglionic fibers release norepinephrine (noradrenaline) which acts on beta one (β₁) adrenergic receptors distributed on cardiac muscle. The circulating epinephrine hormone from adrenal medulla also combines with the same receptors (β₁receptors).

Blood supply of the heart

The myocardial cells receive their blood supply through arteries that branch from the aorta, named coronary arteries.

Coronary veins drain into a single large vein, the coronary sinus, which drain into the right atrium.

The function of the heart valves

The atrioventricular valves (AV valves) are composed of thin membranous cusps (fibrous flaps of tissue covered with endothelium), which hangdown in the ventricular cavities during diastole. After atrial contraction and just before ventricular contraction, the AV valves begin to close and the leaflets (cusps) come together by mean of backflow of the blood in the ventricles towards the atria.

The AV valves include:

· The mitral valve; the left AV valve; bicuspid valve, which consists of two cusps (anterior and posterior), located between left atrium and left ventricle.

· The tricuspid valve; the right AV valve, which consists of three cusps, located between right atrium and right ventricle.

The function of AV valves is to prevent backflow (prevent regurgitation; leakage) of blood into the atria during ventricular contraction. Normally they allow blood to flow from the atrium to the ventricle but prevent backward flow from the ventricle to the atria. The atrioventricular valves contain and supported by papillary muscles.

The aortic and pulmonary valves each consist of three semilunar cusps that resemble pockets projecting into the lumen of aorta and pulmonary trunk. They contaio papillary muscle. During diastole the cusps of these valves become closely approximated to prevent regurgitation of blood from aorta and pulmonary arteries into the ventricles. During systole the cusps are open towards arterial wall, leaving a wide opening for ejection of blood from the ventricles. In other words, the pulmonary and aortic valves allow blood to flow into the arteries during ventricular contraction (systole) but prevent blood from moving in the opposite direction during ventricular relaxation (diastole).

*All valves close and open passively. That is, they close when a backward pressure gradient pushes blood backward, and they open when a forward pressure gradient forces blood in the forward direction.

*There are no valves at entrance of superior, inferior vena cava and pulmonary veins into the atria. What prevents the backflow of blood from the atria toward the veins is the compression of these veins by the atrial contraction. However little blood is ejected back into veins, this represents the venous pulse seen in the neck veins (jugular veins) when the atria contracting.

Function of papillary muscles

The AV valves (mitral and tricuspid) are supported by papillary muscles that attach to the flaps of these valves by the chordae tendineae.The papillary muscles originated from the ventricular walls and contract at the same time when the ventricular walls contract, but these muscles do not help the valves to close or open. Instead, they pull the flaps of the valves inward, toward the ventricles to prevent too much further bulging of the flaps (cusps) backward toward the atria during ventricular contraction, to prevent leakage of blood into the atria (keep the valve flaps tightly closed). In other words, contractions of papillary muscles prevent evertion of the flaps of the AV valves into the atria which could be induced by high pressure produced by contraction of the ventricles.

Figure: Mitral (two cusps) and Aortic (three cusps) valves.

Heart Sounds

When the stethoscope is placed on the chest wall over the heart, two sounds are normally heard during each cardiac cycle (1st & 2nd heart sounds). Heart sounds are associated with closure of the valves with their associated vibration of the flaps of the valves and the surrounding blood under the influence of the sudden pressure changes that develop across the valve. That is, heart sound does not produced by the opening of the valve because this opening is a slow developing process that makes no noise.

1-The first heart sound (S₁): is caused by closure of the AV valves when ventricles contract at systole. The vibration is soft, low-pitched lub.

2-The second heart sound (S₂): is caused by closure of the aortic and pulmonary valves when the ventricles relax at the beginning of diastole. The vibration is loud, high-pitched dup. It is rapid sound because these valves close rapidly and continue for only a short period i.e., rapid, short and of higher pitch dup.

3-The third heart sound (S₃): is caused by rapid filling of the ventricles, by blood that flow with a rumbling motion into the almost filled ventricles; at the middle one third (1/3) of diastole i.e., it is caused by the vibrations of the ventricular walls during the period of rapid ventricular filling that follows the opening of AV valves. It is a low-pitched sound and can be heard after the S₂. It is heard iormal heart; in children and in adult during exercise. It is also heard in anemia, and AV valve regurgitation.

4-The fourth heart sound (S₄): it is an atrial sound when the atria contract (at late diastole). It is a vibration sound (similar to that of S₃) associated with the flow of blood into the ventricle. It is not heard iormal hearts but occurs during ventricular overload as in severe anemia, Thyroitoxicosis (hyperthyroidism) or in reduced ventricular compliance and in hypertension. If present, it is heard before S₁. (S₄, S₁, S₂, S₃).

Heart murmurs

They are abnormal sounds, can be produced by blood flowing rapidly in the usual direction but through an abnormally narrowed valve (stenosis), by blood flowing backward through a damaged, leaky valve (incompetent, regurgitant valve) or by blood flowing between the two atria or two ventricles through a small hole: ASD (atrial septal defect), VSD (ventricular septal defect).

Properties of the cardiac muscle

In addition, to the syncytium property, the cardiac muscle has the property of:

· Automaticity and rhythmicity (Autorhythmicity).

· Excitability and conductivity.

· Contractility

Contractility

Contractility is the ability of the cardiac muscle to contract.

Excitation-Contraction coupling in the heart muscle:

In cardiac muscle, the amount of this activator Ca⁺² is often insufficient to initiate contraction, but it can be increased indirectly by the following mechanism:

1- Active re uptake of Ca⁺² into the sarcoplasmic reticulum by Ca⁺² pump (primary active transport of Ca⁺²).

2- Active pumping of excess Ca⁺² outside the fibres by Na⁺– Ca⁺² exchanger carrier protein (secondary active transport ; counter transport).

Factors that affect cardiac contractility:

· Mechanical

· Cardiac

· Extra cardiac

Mechanical factors:

· Preload (venous return)

· Afterload

The preload:

Frank-Starling’s law of the heart

The Significance of Frank-Starling’s law

The Starling’s law allows autoregulation of myocardial contractility (regulation of the contractility by changing the length of the muscle fibers), in the following conditions:

(2) In denervated hearts (e.g. transplanted hearts); autoregulation of myocardial contractility becomes the main mechanism.

The Afterload:

The afterload is the load that the muscle faces when it begins to contract. In the intact heart, the afterload is produced by the aortic impedance which is determined by:

· The aortic pressure (arterial systolic blood pressure).

· The arterial wall rigidity (arteriosclerosis).

· Blood viscosity (polycythemia).

Cardiac factors:

· The myocardial mass.

· The heart rate.

The myocardial mass:

A significant injury or loss of the functioning ventricular muscle (e.g. due to ischemia or necrosis) decreases the force of myocardial contractility. This also occurs in cases of heart failure.

The heart rate:

Extra cardiac factors:

These factors affect the cardiac inotropic state and they include the following:

· Neural

· Physical

· Chemical

Neural factors:

Sympathetic stimulation and noradrenaline exert a +ve inotropic effect by increasing;

· Cyclic-AMP in the cardiac muscle fibres (which leads to activation of the Ca⁺² channels and more Ca⁺² influx from the ECF).

· The heart rate.

Conversely, parasympathetic stimulation and acetylcholine exert a -ve inotropic effect (by opposite mechanism) but on the atrial muscle only (since the vagi nerves don’t supply the ventricles).

Physical factors:

Chemical factors:

(A) Hormones:

Catecholamines (epinephrine, norepinephrine and dopamine), glucagon and the thyroid hormones; all exert a +ve inotropic effect.

(B) Blood gases:

(D) Inorganic ions:

(E) Toxins:

(F) Drugs:

· Xanthines (e.g., caffeine and theophylline; bronchodilator): They exert a +ve inotropic effect.

· Ouinidine, barbiturates, procainamide (and other anesthetic drugs) as well as Ca⁺² blocker drugs all have a -ve inotropic effect by decreasing Ca⁺² influx into the cardiac muscle fibres.

The Cardiac cycle

The cardiac events that occur from the beginning of one heartbeat to the beginning of the next are called the cardiac cycle. Each cycle is initiated by spontaneous generation of an action potential in the sinus node which travels rapidly through both atria and then through the A-V bundle into the ventricles.

Because of this special arrangement of the conducting system from the atria into the ventricles, there is a delay of more than 0.1 second during passage of the cardiac impulse from the atria into the ventricles. This allows the atria to contract, pumping blood into the ventricles before the strong ventricular contraction begins. Thus, the atria act as primer pumps for the ventricles, and the ventricles in turn provide the major source of power for moving blood through the body’s vascular system.

In a normal heart, cardiac activity is repeated in a regular cycle. At a normal heart rate of about 72 beats/minute; for the atria, the cycle lasts for about 0.15 second in systole and 0.65 second in diastole. For the ventricles, the duration of each cardiac cycle lasts about 0.8 second. If the heart rate increases, the diastole decreases, which means that the heart beating very fast may not remain relaxed long enough to allow complete filling of the ventricles before the next contraction.

For the ventricles, the two major phases of the cardiac cycle are:

· The diastole; a period of ventricular relaxation in which the ventricles fill with blood and it last for about 0.5 second.

· The systole; a period of ventricular contraction and blood ejection, lasting about 0.3 second.

Phases of the cardiac cycle:

The cardiac cycle starts by atrial systole followed by ventricular systole then by diastole of the whole heart.

Atrial systole (atria as a pump):

It is the first phase of cardiac cycle. Blood normally flows continually (passively) from the veins into the atria and about 75% of the blood in the atria flow directly into the ventricles even before the atrial contraction. Then, atrial contraction usually causes an additional 25% filling of the ventricles. So the heart can continue to operate satisfactorily under most condition without this extra 25%, yet this 25% is needed in case of exercise.